AIM:To investigate the effect of AG 490 on the expression of VEGF and HIF-1α, and the capacity of invasion in human erythroleukemia (HEL) cells.METHODS:The HEL cells were treated with AG490 at different con-centrations .The cell viability was detected by CCK-8 assay.The apoptosis was detected by Hoechst staining .The apoptosis and the cell cycle were analyzed by flow cytometry .The capacity of migration was evaluated by Transwell assay .The mRNA expression level of JAK2 was measured by RT-PCR.The protein levels of p-JAK2, VEGF and HIF-1αwere determined by Western blot.RESULTS:The HEL cell viabilities were 88%, 75%, 48%, 10%and 0.12%after treated with AG490 at 20, 40, 60, 80 and 100 μmol/L for 48 h, respectively.The results of Hoechst staining showed that brilliant blue cells in 80 μmol/L AG490 group was significantly increased compared with control group for 48 h.The apoptosis rate of 80μmol/L AG490 group was significantly increased compared with control group at 48 h after AG490 treatment.The number of membrane-permeating HEL cells in 20μmol/L AG490 group at 24 h after AG490 treatment was significantly lower than that in control group (P<0.05).The mRNA level of JAK2 decreased in a concentration-dependent manner after the HEL cells were treated with different concentrations of AG 490 for 48 h.The protein levels of p-JAK2, VEGF and HIF-1αwere lower in AG490 treatment groups than those in control group (P<0.05).CONCLUSION: AG490 inhibits the expression of VEGF and HIF-1αin HEL cells by inhibiting JAK2 pathway.

Objective To evaluate the effect of acupuncture on the quality of recovery during the early period after gynecological laparoscopic surgery using the Quality of Recovery?40 questionnaire ( QoR?40). Methods Sixty patients, aged 20-60 yr, with body mass index of 18.5-28.0 kg∕m2, of American Society of Anesthesiologists physical status ⅠorⅡ, scheduled for elective gynecological laparoscopic surgery, were equally and randomly divided into either control group ( group C ) or acupuncture group (group Acu) using a random number table. Bilateral Neiguan (PC6) and Hegu (L14) acupoints were stimulated for 30 min starting from the time point before skin incision and immediately after the end of surgery. The quality of recovery was assessed using the QoR?40 on 1 day before surgery, and at 24 and 48 h after surgery. The patient′s cognitive function was assessed using Mini?Mental State Examination. The requirement for rescue analgesics was recorded. The occurrence of nausea and vomiting was also recorded. Results Compared with group C, the global QoR?40 and Mini?Mental State Examination scores were significantly increased, and the incidence of nausea and vomiting and requirement for rescue analgesics were decreased at 24 and 48 h after surgery in group Acu ( P<0. 05 ) . Conclusion Acupuncture can improve the quality of recovery during the early period after gynecological laparoscopic surgery using the QoR?40.

Objective To explore the characteristics of cesarean scars pregnancy(CSP)and discuss differ-ent therapeutic methods and clinical outcomes. Methods Clinical data of 96 cases of CSP were collected from Sep-tember 2013 to October 2016 and patients′ clinical features,intra-operative findings,β-HCG,vaginal bleeding duration,hospital stay and cost and effects of different treatments were recorded and analyzed. Results The types of CSP were the determinant of lesion resection ,followed by the tumor size and blood β-HCG levels. The cases of uterine lesion resection and general uterine curettage with UAE had less blood loss than those without UAE. The cases of uterine lesion resection had short hospital stay and those with general uterine curettage had longer vaginal bleeding duration. Conclusion TVCD and MRI have important values in the diagnosis of CSP. During the treatment of CSP,personalized treatment planning,early diagnosis and treatment exert influence on reducing complications.

Objective To study serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and its correlation with accumulation degree of 99Tcm-MDP on bone and arthritis and to study the role of sICAM-1 in the diagnosis of patients with early RA. Methods Serum levels of sICAM-1 were measured by immunoenzymetic assay (ELISA). 99mTc-MDP scintigraphy was carried out for the same patients. The significant test between serum levels of sICAM-1 of three groups was performed with analysis of variance; Correlations between serum levels of sICAM-1 and index of semiquatitive 99Tcm-MDP were obtained using sperman's ranks correlation method. Results Compared with control group,serum levels of sICAM-1 were significantly higher in standard group (group A) (P<0.01) and non-standard group (group B) (P<0.05). No significant difference was found between group A and B(P>0.05). Serum levels of sICAM-1 were positively correlated with 99Tcm-MDP scintigraphy. Most patients of non-standard group and standard group showed visible medium-high uptake of 99Tcm-MDP. While control group had not obviously uptake of 99Tcm-MDP. Conclusion Serum levels of sICAM-1, semiquatitive 99Tcm-MDP scintigraphy, accumulation degree of radiopharmuceuutial on bone and arthritis are helpful for diagnosis of early rheumatoid arthritis and judge-ment of the clinical status and improvement of the prognosis.

Objective: To investigate the regulation of JAK2 tyrosine kinase inhibitor ruxolitinib on extracellular matrix metalloproteinase (MMP in JAK2V617F positive myeloproliferative neoplasms (MPN) cells. Methods: ①Forty cases of newly diagnosed JAK2V617F positive MPN patients and 15 healthy volunteers as control in Baoding No.1 Hospital between January 2012 and December 2015 were enrolled in this study. JAK2V617F/JAK2 ratio was detected by real-time-PCR; the expression levels of phosphorylation protein tyrosine kinase 2 (p-JAK2) , MMP-2 and MMP-9 in pathological tissues of bone marrow were detected by immunohistochemistry. The bone marrow cells of JAK2V617F positive MPN patients were treated with ruxolitinib, then the migration ability and MMP-2, MMP-9 gene and protein expression levels were detected. ②The human erythroleukemia cell line HEL cells were treated with different concentrations of ruxolitinib (0, 50, 100, 250, 500, 1 000 nmol/L) . The cell viability was detected by CCK-8 test; cell migration ability was tested by transwell chambers. The mRNA expression levels of JAK2, MMP-2 and MMP-9 were detected by real-time-PCR. The protein expression levels of p-JAK2, MMP-2 and MMP-9 were detected by Western blot. Results: ①The expression levels of p-JAK2, MMP-2 and MMP-9 in the newly diagnosed group were significantly higher than control group respectively [ (78.56±24.55) % vs (41.59±17.29) %, P<0.05; (48.25±18.74) % vs (22.79±13.89) %, P<0.05; (53.29±19.28) % vs (15.56±14.96) %, P<0.05]. Spearman correlation analysis showed the positive correlation of MMP-2 and MMP-9 protein expression levels with JAK2V617F mutation (r=0.526, P=0.001; r=0.543, P=0.001) . ②The proliferation of HEL cells was inhibited by different concentrations of ruxolitinib in time and dose dependent manner. ③Cell migration test showed the number of cells leaked to the low chamber in MPN patients bone marrow cells and HEL cells treated with 5 nmol/L of ruxolitinib group were significantly lower than that without ruxolitinib treatment after 24 h [ (154.7±27.5) vs (320.3±67.3) , t=13.47, P<0.05; (70.7±10.5) vs (135.3±16.7) , t=13.89, P<0.05]. The mRNA and protein expression levels of JAK2, MMP-2 and MMP-9 decreased with the increased concentration of ruxolitinib. Conclusion Ruxolitinib inhibits MPN cell migration and expression of MMP-2 and MMP-9 via JAK2 signal pathway.

Objective:To compare the efficacy between laparoscopy and open surgery for gastric gastrointestinal stromal tumor (GIST) larger than 2 cm.Methods:A multicenter retrospective cohort study was performed. Inclusion criteria: long diameter of primary gastric GIST > 2 cm; undergoing laparoscopy or open surgery; diagnosis confirmed by postoperative pathology without distant metastasis; without preoperative targeted therapy. Clinicopathological data of 857 gastric GIST patients, including 320 in PLA General Hospital, 284 in Shanghai Renji Hospital, 175 in Wuhan Union Hospital and 78 in Tianjin Cancer Hospital, from January 2010 to May 2017 were retrospectively collected. There were 418 males and 439 females, mainly aged between 50 and 70 years old. Among 857 patients, 413 were in the laparoscopy group and 444 in the open group. The nearest neighbor matching of propensity score matching method was conducted with 1:1 matching based on tumor location and size between laparoscopy and open group to obtain samples of covariate equilibrium, and the caliper value was 0.04. The t test, χ 2 test and Wilcoxon rank test were used to compare short-term efficacy, and the Kaplan-Meier curve and log rank test were applied to compare long-term outcomes between the two groups. Results:After propensity score matching, laparoscopy group and open group both enrolled 293 cases. The baseline data, including age, gender, tumor location, tumor long diameter, NIH classification, etc. were not significantly different between the two groups (all P>0.05). Compared with the open group, the laparoscopy group had less intraoperative blood loss [<100 ml: 2.9% (155/293) vs. 36.2% (106/293), Z=-12.857, P<0.001], shorter time to postoperative feeding [(4.0±0.2) days vs. (5.3±0.9) days, t=1.505, P=0.003] and to the removal of drainage tube [(4.8±1.0) days vs. (6.5±1.0) days, t=1.847, P=0.008], and shorter postoperative hospital stay [(8.6±0.3) days vs. (10.5±0.3) days, t=4.235, P<0.001]. Subgroups analysis according to anatomical location: (1) Gastric cardia and pylorus: there were no statistically significant differences in perioperative parameters between the two groups (all P>0.05). (2) Stomach base: feeding time after surgery [(4.0±0.2) days vs. (4.5±0.2) days, t=0.512, P=0.038], drainage tube removal time [(5.1±0.4) days vs. (6.4±0.6) days, t=0.517, P=0.044], postoperative hospital stay [(8.0±0.5) days vs. (11.1±0.9) days, t=0.500, P=0.002] were all significantly shorter in the laparoscopy group as compared to the open group, while the differences in other perioperative parameters were not statistically significant (all P>0.05). (3) Lesser curvature of the stomach: the laparoscopy group had less intraoperative blood loss [<100 ml ratio: 58.1% (43/74) vs. 33.7% (25/74), Z=7.632, P=0.034], shorter gastric tube removal time [(2.7±0.2) days vs. (3.2±0.3) days, t=0.503, P=0.007], earlier postoperative passage of gas [(2.8±0.1) days vs. (3.4±0.2) days, t=0.532, P=0.030], earlier postoperative feeding [(3.6±0.2) days vs. (4.3±0.2) days, t=0.508, P=0.020], shorter drainage tube removal time [(4.2±0.4) days vs. (5.7±0.5) days, t=0.508, P=0.020] and postoperative hospital stay [(8.3±0.6) days vs. (10.7±0.3) days, t=0.502, P=0.006] as compared to the open group. (4) Great curvature of the stomach: the laparoscopy group presented less intraoperative blood loss [<100 ml ratio: 52.7% (39/74) vs. 36.5% (27/74), Z=7.681, P=0.032], earlier gastric tube removal [(2.6±0.2) days vs. (3.6±0.2) days, t=0.501, P=0.001], earlier postoperative passage of gas [(2.7±0.2) days vs. (3.4±0.2) days, t=0.501, P=0.016], earlier postoperative feeding [(3.6±0.2) days vs. (4.7±0.2) days, t=0.500, P=0.001], shorter drainage tube removal time [(4.0±0.5) days to (5.9±0.4) days, t=0.508, P=0.002] and postoperative hospital stay [(7.5±0.3) days to (9.5±0.1) days, t=0.500, P=0.001] than the open group. Subgroup analysis according to tumor size: (1) Tumor long diameter 2.0-5.0 cm: the laparoscopy group had earlier passage of gas [(2.9±0.1) days vs. (3.5±0.1) days, t=0.500, P=0.001], earlier postoperative feeding [(4.5±0.1) days vs. (5.0±0.2) days, t=0.501, P=0.013], shorter drainage tube removal time [(4.8±0.3) days vs. (6.0±0.3) days, t=0.511, P=0.008] and postoperative hospital stay [(8.1±0.4) days to (10.1±0.3) days, t=0.513, P=0.001] than the open group. (2) Tumor long diameter 5.1-10.0 cm: in the laparoscopic group, postoperative feeding time [(4.0±0.2) days vs. (4.7±0.2) days, t=0.506, P=0.015], drainage tube removal time [(4.6±0.4) days vs. (6.4±0.5)) days, t=0.501, P=0.004], postoperative hospital stay [(8.2±0.3) days vs. (10.9±0.6) days, t=0.500, P=0.001] were all shorter than those in the open group. No intraoperative and postoperative complications were observed in each group. The 5-year recurrence-free survival rates of the laparoscopy group and the open group were 95.4% and 91.6%, respectively ( P=0.734), and the 5-year overall survival rates were 93.8% and 90.8% ( P=0.691), respectively, and the differences were not statistically significant. Conclusions:In experienced medical centers, laparoscopic surgery for gastric GIST larger than 2 cm is safe and feasible, and can achieve comparable efficacy with open surgery. For gastric GISTs which do not locate in the greater curvature and the anterior wall of the stomach, and whose long diameter is ≤5 cm, laparoscopic surgery does not increase the risk of recurrence and metastasis, and can accelerate postoperative recovery.

Objective:To compare the efficacy between laparoscopy and open surgery for gastric gastrointestinal stromal tumor (GIST) larger than 2 cm.Methods:A multicenter retrospective cohort study was performed. Inclusion criteria: long diameter of primary gastric GIST > 2 cm; undergoing laparoscopy or open surgery; diagnosis confirmed by postoperative pathology without distant metastasis; without preoperative targeted therapy. Clinicopathological data of 857 gastric GIST patients, including 320 in PLA General Hospital, 284 in Shanghai Renji Hospital, 175 in Wuhan Union Hospital and 78 in Tianjin Cancer Hospital, from January 2010 to May 2017 were retrospectively collected. There were 418 males and 439 females, mainly aged between 50 and 70 years old. Among 857 patients, 413 were in the laparoscopy group and 444 in the open group. The nearest neighbor matching of propensity score matching method was conducted with 1:1 matching based on tumor location and size between laparoscopy and open group to obtain samples of covariate equilibrium, and the caliper value was 0.04. The t test, χ 2 test and Wilcoxon rank test were used to compare short-term efficacy, and the Kaplan-Meier curve and log rank test were applied to compare long-term outcomes between the two groups. Results:After propensity score matching, laparoscopy group and open group both enrolled 293 cases. The baseline data, including age, gender, tumor location, tumor long diameter, NIH classification, etc. were not significantly different between the two groups (all P>0.05). Compared with the open group, the laparoscopy group had less intraoperative blood loss [<100 ml: 2.9% (155/293) vs. 36.2% (106/293), Z=-12.857, P<0.001], shorter time to postoperative feeding [(4.0±0.2) days vs. (5.3±0.9) days, t=1.505, P=0.003] and to the removal of drainage tube [(4.8±1.0) days vs. (6.5±1.0) days, t=1.847, P=0.008], and shorter postoperative hospital stay [(8.6±0.3) days vs. (10.5±0.3) days, t=4.235, P<0.001]. Subgroups analysis according to anatomical location: (1) Gastric cardia and pylorus: there were no statistically significant differences in perioperative parameters between the two groups (all P>0.05). (2) Stomach base: feeding time after surgery [(4.0±0.2) days vs. (4.5±0.2) days, t=0.512, P=0.038], drainage tube removal time [(5.1±0.4) days vs. (6.4±0.6) days, t=0.517, P=0.044], postoperative hospital stay [(8.0±0.5) days vs. (11.1±0.9) days, t=0.500, P=0.002] were all significantly shorter in the laparoscopy group as compared to the open group, while the differences in other perioperative parameters were not statistically significant (all P>0.05). (3) Lesser curvature of the stomach: the laparoscopy group had less intraoperative blood loss [<100 ml ratio: 58.1% (43/74) vs. 33.7% (25/74), Z=7.632, P=0.034], shorter gastric tube removal time [(2.7±0.2) days vs. (3.2±0.3) days, t=0.503, P=0.007], earlier postoperative passage of gas [(2.8±0.1) days vs. (3.4±0.2) days, t=0.532, P=0.030], earlier postoperative feeding [(3.6±0.2) days vs. (4.3±0.2) days, t=0.508, P=0.020], shorter drainage tube removal time [(4.2±0.4) days vs. (5.7±0.5) days, t=0.508, P=0.020] and postoperative hospital stay [(8.3±0.6) days vs. (10.7±0.3) days, t=0.502, P=0.006] as compared to the open group. (4) Great curvature of the stomach: the laparoscopy group presented less intraoperative blood loss [<100 ml ratio: 52.7% (39/74) vs. 36.5% (27/74), Z=7.681, P=0.032], earlier gastric tube removal [(2.6±0.2) days vs. (3.6±0.2) days, t=0.501, P=0.001], earlier postoperative passage of gas [(2.7±0.2) days vs. (3.4±0.2) days, t=0.501, P=0.016], earlier postoperative feeding [(3.6±0.2) days vs. (4.7±0.2) days, t=0.500, P=0.001], shorter drainage tube removal time [(4.0±0.5) days to (5.9±0.4) days, t=0.508, P=0.002] and postoperative hospital stay [(7.5±0.3) days to (9.5±0.1) days, t=0.500, P=0.001] than the open group. Subgroup analysis according to tumor size: (1) Tumor long diameter 2.0-5.0 cm: the laparoscopy group had earlier passage of gas [(2.9±0.1) days vs. (3.5±0.1) days, t=0.500, P=0.001], earlier postoperative feeding [(4.5±0.1) days vs. (5.0±0.2) days, t=0.501, P=0.013], shorter drainage tube removal time [(4.8±0.3) days vs. (6.0±0.3) days, t=0.511, P=0.008] and postoperative hospital stay [(8.1±0.4) days to (10.1±0.3) days, t=0.513, P=0.001] than the open group. (2) Tumor long diameter 5.1-10.0 cm: in the laparoscopic group, postoperative feeding time [(4.0±0.2) days vs. (4.7±0.2) days, t=0.506, P=0.015], drainage tube removal time [(4.6±0.4) days vs. (6.4±0.5)) days, t=0.501, P=0.004], postoperative hospital stay [(8.2±0.3) days vs. (10.9±0.6) days, t=0.500, P=0.001] were all shorter than those in the open group. No intraoperative and postoperative complications were observed in each group. The 5-year recurrence-free survival rates of the laparoscopy group and the open group were 95.4% and 91.6%, respectively ( P=0.734), and the 5-year overall survival rates were 93.8% and 90.8% ( P=0.691), respectively, and the differences were not statistically significant. Conclusions:In experienced medical centers, laparoscopic surgery for gastric GIST larger than 2 cm is safe and feasible, and can achieve comparable efficacy with open surgery. For gastric GISTs which do not locate in the greater curvature and the anterior wall of the stomach, and whose long diameter is ≤5 cm, laparoscopic surgery does not increase the risk of recurrence and metastasis, and can accelerate postoperative recovery.

Objective:To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI +）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods:Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results:(1) A total of 4 891 patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.367, 95% CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS ( HR=1.420, 95% CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS ( P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups ( P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.705, 95% CI: 1.088-2.674, P=0.020). Conclusions:For patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.